Deuterium Metabolic Imaging – Back to the Future
Robin A. de Graaf1
1Yale University School of Medicine, New Haven, CT, United States

Synopsis

Deuterium metabolic imaging (DMI) is a robust MR-based method to image active metabolism non-invasively in vivo. The metabolic conversion of deuterated glucose into metabolic products (lactate, glutamate) can be followed dynamically for absolute metabolic rate mapping or detected at steady-state for high-contrast metabolic images of aberrant metabolism in pathologies such as tumors and stroke. The high sensitivity, robust acquisition methods, availability of affordable deuterated substrates and the option for time-efficient, interleaved acquisition of DMI and MRI, combine into a highly robust metabolic imaging method with strong potential to become a dominant MR research tool and a viable clinical imaging modality.

Non-invasive imaging of metabolic pathways in neurological disease has been a long-standing goal to monitor disease progression or therapy efficacy. FDG-PET and 1H, 13C and 31P MR-based spectroscopic imaging (MRSI) are most commonly employed, whereby each method has specific considerations related to achievable image contrast, robustness, reproducibility and availability.
Deuterium (2H) has long been recognized as a powerful metabolic tracer (1). The favorable MR characteristics of 2H (large magnetic moment, short T1s while retaining sufficient spectral resolution, low natural abundance) have been utilized for blood flow and perfusion mapping ((2), see lecture by J. J. H. Ackerman). Metabolism of 2H-labeled substrates has been demonstrated sporadically (3-9), cumulating in the high-sensitivity, high-field detection of 2H-glucose metabolism in rat brain in vivo (10,11). Deuterium Metabolic Imaging (DMI) capitalizes on the high-sensitivity of 2H MR by detecting the 2H-labeled substrates and metabolic products as 3D spatial maps. First-in-human DMI studies of glucose metabolism in healthy brain and in patients with high grade brain tumors illustrate high-contrast maps of glucose, glutamate and lactate (11). DMI can use a range of deuterated substrates (acetate, choline, fumarate, glucose) (11-15), has demonstrated exceptional sensitivity and resolution at ultra-high-fields (16,17) and can be acquired in a time-efficient, interleaved manner with MRI (18). With technically simple and robust methods, clinically relevant demonstrations and building on the foundations from the past (19), the future of DMI looks very bright.

Acknowledgements

This work was funded in part by NIH grant R01-EB025840.

References

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Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)